Tracking the spread of a lacZ-tagged herpes simplex virus type 1 between the eye and the nervous system of the mouse:: Comparison of primary and recurrent infection

The spread of herpes simplex virus type 1 (HSV-1) during primary ocular infection and after reactivation of latent infection in the trigeminal ganglion (TG) was examined in the mouse using a genetically modified virus containing the lacZ reporter gene under the control of the immediate-early 110 promoter, Whole tissue mounts of the eye and lids, their sensory nerves, and TG with the attached dorsal root entry zone (DRE) into the central nervous system (CNS) were stained for beta -galactosidase. Sixteen hours after inoculation of the cornea by scarification, staining was found in the scarified epithelium of the cornea and in the unscarified conjunctiva. By 24 h, staining was also seen in a few TG neurons and by 96 h their number had greatly increased and their distribution was more widespread. Stained cells (identified as Schwann cells by their staining for glial fibrillary acidic protein [GFAP] or S-100) in the TG were first seen close to stained neurons at 40 h, and by 48 h lines of such cells extended partway toward the periphery and toward the DRE, By 72 h, these lines had reached the periphery and the DRE where the adjacent CNS was also stained. In the cornea, stained cells with the morphology and arrangement of Schwann cells were seen from 40 to 120 h, After reactivation of latent infection, 10 of 22 samples had positively stained neurons. In eight samples, corneal and lid epithelial cells were stained. No stained Schwann cells were seen in the TG; however, branched networks of such cells were present in the cornea and the lids. This detailed sequential analysis has provided new information on the involvement of Schwann cells in the pathogenesis of primary and recurrent HSV-1 disease in the TG and the cornea.